1. Field of the Invention
The present invention relates generally to usage of proximal probes of atomic-scale precision for interactions with molecules.
2. Description of Related Art
Research discoveries continue to advance the knowledge of nanotechnology. Scientists are venturing into the realm of the almost indescribably tiny. In nanotechnology, everything can be described in terms of atomic interactions. At these dimensions, the distinctions between biology and physics are blurring, which increases the difficulty of nanotechnology because, despite the number of advances, scientists in their respective disciplines are encroaching upon each other's research domains. For example, to make tiny electronic circuits, some physicists have tried to mimic nature by causing inanimate matter to assemble itself in a manner that resembles biological processes.
The manipulation of matter at the atomic level is not new. In 1981, Gerd Binnig and Heinrich Rohrer at the IBM Research Laboratory in Zurich, Switzerland, invented and patented the scanning tunneling microscope (STM) (U.S. Pat. No. 4,343,993, herein incorporated by reference in its entirety for all purposes), which greatly advanced the ability to understand the microscopic world at the atomic level. The key component of an STM is an extremely sharp tip made from a metal such as tungsten mounted on an array of piezoelectric elements which control the tip's position in three dimensions. The STM can spatially control the tip very precisely, such as on the order of a nanometer with respect to a surface. At such tiny distances, currents can tunnel between the tip and the surface. As the tip is moved across the surface of the sample, its height is adjusted to keep the tunneling current at a constant amount such that the STM can image the electron clouds of the surface atoms in the sample. With pictures of the surface of inorganic materials such as metal and semiconductors, the STM gave scientists their first vision of the nanoworld. This work won Binnig and Rohrer the Nobel prize in 1986.
Despite its capabilities, the STM is limited to imaging conducting materials. To overcome this limitation, Binnig and others developed a related device to the STM called an atomic force microscope (AFM). This now well-known device senses the topography of a sample using a tiny tip mounted on the end of a minuscule, microfabricated cantilever. Rather than using the tunneling current, the sample is scanned by actually bringing the tip in contact with the sample surface, and the interaction of atomic forces between the nanometer-sharp tip and the sample surface causes pivotal deflections of the cantilever. The AFM measures the minute upward and downward deflections needed to maintain a constant force of contact. As the AFM relies on contact force, it can be used to image nonconducting materials such as organic or insulating materials.
Other variants of the STM and AFM have been developed. These devices can probe other aspects of materials at the molecular level such as magnetic and electrostatic forces, van der Waals interactions, temperature variations, optical absorption, near-field optics, and acoustics. These are collectively known as “proximal probes”; a variety of these probes are described in Pool, “Children of the STM”, Science, v. 247, pp. 634–636 (1990).
As soon as scientists could see individual atoms, they could not resist playing with them. Proximal probe devices have been used to manipulate atoms and molecules essentially by picking them up with the scanning tip and moving them; e.g., see D. M. Eigler and E. K. Schweizer, “Positioning Single Atoms with a Scanning Tunneling Microscope”, Nature, v. 344, pp. 524–526 (1990), which describes the positioning of xenon atoms on a nickel substrate to form the initials “IBM”. Other STM images can be found in “STM Rounds Up Electron Waves at the QM Corral”, Physics Today, v. 46, n. 11, pp. 17–19 (1993).
IBM and others have developed new applications for proximal probes technologies. With a team of colleagues in Zurich, Binnig has created a nanoscopic brush with over a thousand tiny tips, each on its own cantilever, in a “millipede” storage system. Using heater cantilevers, dents are made in a polymer material; such thermomechanical recording has been demonstrated at 400 gigabytes per square inch storage density. The tips are used for reading the dents as well; data rates of a few megabytes per second for reading and 100 kilobytes per second for writing have been demonstrated, as described in Binnig et al., “Ultrahigh-density Atomic Force Microscopy Data Storage with Erase Capability”, Applied Physics Letter, v. 74, n. 9, pp. 1329–1331, May, 1, 1999, and Vettinger et al., “The Millipede—More Than One Thousand Tips for Future AFM Data Storage”, IBM Journal of Research & Development, v. 44, n. 3, pp. 323–340, May 2000. A magnetic millipede which uses a magnetic substrate is described in Allenspach et al., U.S. Pat. No. 6,680,808, “Magnetic Millipede for Ultra High Density Magnetic Storage”, herein incorporated by reference in its entirety for all purposes.
While most of Binnig's work has been based on mechanical principles, others are using natural processes for insights on how to manipulate matter. Angela Belcher at the University of Texas has used proteins to build new semiconductor materials. As an example, she studied abalone shell, which despite being made of two types of chalk, is about 3000 times as strong as the chalk found in rock; it is proteins produced by the abalone's RNA which determine how to optimally arrange the chalk molecules. Using this insight, she has assembled a set of proteins which control crystal growth in various ways. Some of this research is described in “Selection of Peptides with Semiconductor Binding Specificity for Directed Nanocrystal Assembly”, Nature, v. 405, pp. 666–668 (8 Jun. 2000).
Like Belcher, Heller et al. has used chemical chains to interact with other molecules, as described in U.S. Pat. No. 5,605,662, “Active Programmable Electronic Devices for Molecular Biological Analysis and Diagnosis”. In Heller et al., the chains are held in place by an array of microlocations (much larger than individual molecule size) which are set up to hold different chemical agents at each site which in turn bind to the molecules of interest. While this permits interesting programmability of what molecules are concentrated in which area, it does not manipulate the molecules individually but rather in bulk. Belcher and Heller et al. do not directly manipulate the molecules but rather indirectly affect the molecules using analytes, proteins, or their equivalents.
Researchers have also proposed combining the selection qualities of organic molecules and the positioning precision of proximal probes. Eric Drexler in Nanosystems: Molecular Machinery, Manufacturing, and Computation, Wiley Interscience (1992), proposed an AFM having multiple bead bound worksites comprising organic molecules on the probe surface. Harold Craighead and his team at Cornell University have attached antibodies to a proximal probe on a cantilever. With this device, they can detect the presence of particular bacteria. If present, the antibodies bond to the bacteria; as the probe is weighed down by the accumulation of bacteria, the resonant frequency of the vibrating cantilever is changed.
In living beings, most manipulations are driven by DNA, RNA, and special proteins which work on the principle of creating an electrostatic pattern of charges which closely match the complementary pattern of charges on the molecule to be manipulated, thereby allowing the appropriate molecule to be attached to an enzyme, catalyst, or other manipulating molecule. It would be advantageous to provide the ability to perform similar types of molecular manipulation using proximal probe technology.